Genetic control of thymic NKT cell number

胸腺 NKT 细胞数量的遗传控制

• 批准号: nhmrc : 379608
• 负责人: Prof Alan Baxter
• 金额: $ 59.48万
• 依托单位: James Cook University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/genetic-control-thymic-cell-number/78137
• 关键词: Genetic; control; thymic; NKT; cell

Autoimmune diseases result from a complex interaction between multiple genes and environmental factors. Attempts to identify the genes involved have been largely unsuccessful because of this complexity. This project has chosen to focus on a particular subset of the genes that cause type 1 (autoimmune) diabetes - the subset that control a small population of regulatory white blood cells, termed NKT cells. The applicants have previously shown that a mouse strain prone to diabetes, the NOD mouse strain, is deficient in NKT cells and if they are replaced by transfusion, the mice are protected from disease. In selective breeding experiments, they have been able to show that the deficiency in NKT cell numbers is genetic, and have localised the chromosomal positions of these genes. Furthermore, they have produced specially bred lines of NOD mice that have normal copies of these genes and increased numbers of NKT cells. This project aims to identify the genetic coding sequences responsible for controlling numbers of NKT cells. It will use a combination of genetic mapping, specific breeding, gene analyses and the production of genetically modified organisms. The result of this study will be the identification of at least one of the genes that control NKT cell numbers. These gene(s) will then be studied in patients to determine if it plays a role in human disease.

自身免疫性疾病是多基因和环境因素复杂相互作用的结果。由于这种复杂性，识别相关基因的尝试在很大程度上没有成功。该项目选择专注于导致1型(自身免疫性)糖尿病的特定基因子集-控制一小部分调节性白细胞的子集，称为NKT细胞。申请人之前已经证明，一种易患糖尿病的小鼠品系NOD小鼠品系缺乏NKT细胞，如果它们被输血取代，小鼠就能免受疾病的侵袭。在选择性育种实验中，他们已经能够证明NKT细胞数量的不足是遗传的，并定位了这些基因的染色体位置。此外，他们还培育了专门培育的NOD小鼠品系，这些品系具有这些基因的正常拷贝和增加的NKT细胞数量。该项目旨在确定负责控制NKT细胞数量的遗传编码序列。它将使用遗传图谱、特定育种、基因分析和转基因生物生产的组合。这项研究的结果将是确定至少一个控制NKT细胞数量的基因。这些基因(S)随后将在患者身上进行研究，以确定它是否在人类疾病中发挥作用。